Lung toxicity, deposition, and clearance of thermal spray coating particles with different metal profiles after inhalation in rats.

Thermal spray coating is a process in which molten metal is sprayed onto a surface. Little is known about the health effects associated with these aerosols. Sprague-Dawley rats were exposed to aerosols (25 mg/m3 × 4 hr/d × 4 d) generated during thermal spray coating using different consumables [i.e. stainless-steel wire (PMET731), Ni-based wire (PMET885), Zn-based wire (PMET540)]. Control animals received air. Bronchoalveolar lavage was performed at 4 and 30 d post-exposure to assess lung toxicity. The particles were chain-like agglomerates and similar in size (310-378 nm). Inhalation of PMET885 aerosol caused a significant increase in lung injury and inflammation at both time points. Inhalation of PMET540 aerosol caused a slight but significant increase in lung toxicity at 4 but not 30 d. Exposure to PMET731 aerosol had no effect on lung toxicity. Overall, the lung responses were in the order: PMET885≫PMET540 >PMT731. Following a shorter exposure (25 mg/m3 × 4 h/d × 1d), lung burdens of metals from the different aerosols were determined by ICP-AES at 0, 1, 4 and 30 d post-exposure. Zn was cleared from the lungs at the fastest rate with complete clearance by 4 d post-exposure. Ni, Cr, and Mn had similar rates of clearance as nearly half of the deposited metal was cleared by 4 d. A small but significant percentage of each of these metals persisted in the lungs at 30 d. The pulmonary clearance of Fe was difficult to assess because of inherently high levels of Fe in control lungs.

In vivo and in vitro toxicity of a stainless-steel aerosol generated during thermal spray coating.

Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague-Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/m3 × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0-200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days.

Development of a thermal spray coating aerosol generator and inhalation exposure system.

Thermal spray coating involves spraying a product (oftentimes metal) that is melted by extremely high temperatures and then applied under pressure onto a surface. Large amounts of a complex metal aerosol (e.g., Fe, Cr, Ni, Zn) are formed during the process, presenting a potentially serious risk to the operator. Information about the health effects associated with exposure to these aerosols is lacking. Even less is known about the chemical and physical properties of these aerosols. The goal was to develop and test an automated thermal spray coating aerosol generator and inhalation exposure system that would simulate workplace exposures. An electric arc wire-thermal spray coating aerosol generator and exposure system was designed and separated into two areas: (1) an enclosed room where the spray coating occurs; (2) an exposure chamber with different measurement devices and controllers. The physicochemical properties of aerosols generated during electric arc wire-thermal spray coating using five different consumable wires were examined. The metal composition of each was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES), including two stainless-steel wires [PMET720 (82 % Fe, 13 % Cr); PMET731(66 % Fe, 26 % Cr)], two Ni-based wires [PMET876 (55 % Ni, 17 % Cr); PMET885 (97 % Ni)], and one Zn-based wire [PMET540 (99 % Zn)]. The particles generated regardless of composition were poorly soluble, complex metal oxides and mostly arranged as chain-like agglomerates and similar in size distribution as determined by micro-orifice uniform deposit impactor (MOUDI) and electrical low-pressure impactor (ELPI). To allow for continuous, sequential spray coating during a 4-hr exposure period, a motor rotated the metal pipe to be coated in a circular and up-and-down direction. In a pilot animal study, male Sprague-Dawley rats were exposed to aerosols (25 mg/m3 × 4 h/d × 9 d) generated from electric arc wire- thermal spray coating using the stainless-steel PMET720 consumable wire. The targeted exposure chamber concentration was achieved and maintained during a 4-hr period. At 1 d after exposure, lung injury and inflammation were significantly elevated in the group exposed to the thermal spray coating aerosol compared to the air control group. The system was designed and constructed for future animal exposure studies to generate continuous metal spray coating aerosols at a targeted concentration for extended periods of time without interruption.

Review of the physicochemical properties and associated health effects of aerosols generated during thermal spray coating processes.

Thermal spray coating is a process that applies a molten metal product under pressure onto a surface. Although thermal spray processes have been used for decades, exposure to aerosols formed during thermal spray coating is an emerging risk. Reports indicate that high concentrations of aerosols composed of toxic metals (e.g. chromium) are generated in the workplace. A knowledge gap exists related to the physicochemical properties of thermal spray coating aerosols as well as any potential associated health effects. The objective of this manuscript was to review thermal spray coating and previous studies that have examined the aerosols produced from this process. A thermal spray coating generator and exposure system is also described that has recently been developed to further evaluate the physical and chemical properties of aerosols formed during thermal spray coating as well as to assess the possible health effects of this process in an effort to mitigate potential occupational health hazards related to the industry.

Aerosol characterization and pulmonary responses in rats after short-term inhalation of fumes generated during resistance spot welding of galvanized steel.

Resistance spot welding is a common process to join metals in the automotive industry. Adhesives are often used as sealers to seams of metals that are joined. Anti-spatter compounds sometimes are sprayed onto metals to be welded to improve the weldability. Spot welding produces complex aerosols composed of metal and volatile compounds (VOCs) which can cause lung disease in workers. Male Sprague-Dawley rats (n = 12/treatment group) were exposed by inhalation to 25 mg/m3 of aerosol for 4 h/day × 8 days during spot welding of galvanized zinc (Zn)-coated steel in the presence or absence of a glue or anti-spatter spray. Controls were exposed to filtered air. Particle size distribution and chemical composition of the generated aerosol were determined. At 1 and 7 days after exposure, bronchoalveolar lavage (BAL) was performed to assess lung toxicity. The generated particles mostly were in the submicron size range with a significant number of nanometer-sized particles formed. The primary metals present in the fumes were Fe (72.5%) and Zn (26.3%). The addition of the anti-spatter spray and glue did affect particle size distribution when spot welding galvanized steel, whereas they had no effect on metal composition. Multiple VOCs (e.g., methyl methacrylate, acetaldehyde, ethanol, acetone, benzene, xylene) were identified when spot welding using either the glue or the anti-spatter spray that were not present when welding alone. Markers of lung injury (BAL lactate dehydrogenase) and inflammation (total BAL cells/neutrophils and cytokines/chemokines) were significantly elevated compared to controls 1 day after exposure to the spot welding fumes. The elevated pulmonary response was transient as lung toxicity mostly returned to control values by 7 days. The VOCs or the concentrations that they were generated during the animal exposures had no measurable effect on the pulmonary responses. Inhalation of galvanized spot welding fumes caused acute lung toxicity most likely due to the short-term exposure of particles that contain Zn.

In Vivo Toxicity Assessment of Occupational Components of the Carbon Nanotube Life Cycle To Provide Context to Potential Health Effects.

Pulmonary toxicity studies on carbon nanotubes focus primarily on as-produced materials and rarely are guided by a life cycle perspective or integration with exposure assessment. Understanding toxicity beyond the as-produced, or pure native material, is critical, due to modifications needed to overcome barriers to commercialization of applications. In the first series of studies, the toxicity of as-produced carbon nanotubes and their polymer-coated counterparts was evaluated in reference to exposure assessment, material characterization, and stability of the polymer coating in biological fluids. The second series of studies examined the toxicity of aerosols generated from sanding polymer-coated carbon-nanotube-embedded or neat composites. Postproduction modification by polymer coating did not enhance pulmonary injury, inflammation, and pathology or in vitro genotoxicity of as-produced carbon nanotubes, and for a particular coating, toxicity was significantly attenuated. The aerosols generated from sanding composites embedded with polymer-coated carbon nanotubes contained no evidence of free nanotubes. The percent weight incorporation of polymer-coated carbon nanotubes, 0.15% or 3% by mass, and composite matrix utilized altered the particle size distribution and, in certain circumstances, influenced acute in vivo toxicity. Our study provides perspective that, while the number of workers and consumers increases along the life cycle, toxicity and/or potential for exposure to the as-produced material may greatly diminish.

Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes.

Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson's disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m(3); 3h/day × 5 d/week × 2 weeks) to fumes generated by gas-metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks.

Neurotoxicity following acute inhalation of aerosols generated during resistance spot weld-bonding of carbon steel.

Welding generates complex metal aerosols, inhalation of which is linked to adverse health effects among welders. An important health concern of welding fume (WF) exposure is neurological dysfunction akin to Parkinson's disease (PD). Some applications in manufacturing industry employ a variant welding technology known as "weld-bonding" that utilizes resistance spot welding, in combination with adhesives, for metal-to-metal welding. The presence of adhesives raises additional concerns about worker exposure to potentially toxic components like Methyl Methacrylate, Bisphenol A and volatile organic compounds (VOCs). Here, we investigated the potential neurotoxicological effects of exposure to welding aerosols generated during weld-bonding. Male Sprague-Dawley rats were exposed (25 mg/m³ targeted concentration; 4 h/day × 13 days) by whole-body inhalation to filtered air or aerosols generated by either weld-bonding with sparking (high metal, low VOCs; HM) or without sparking (low metal; high VOCs; LM). Fumes generated under these conditions exhibited complex aerosols that contained both metal oxide particulates and VOCs. LM aerosols contained a greater fraction of VOCs than HM, which comprised largely metal particulates of ultrafine morphology. Short-term exposure to LM aerosols caused distinct changes in the levels of the neurotransmitters, dopamine (DA) and serotonin (5-HT), in various brain areas examined. LM aerosols also specifically decreased the mRNA expression of the olfactory marker protein (Omp) and tyrosine hydroxylase (Th) in the olfactory bulb. Consistent with the decrease in Th, LM also reduced the expression of dopamine transporter (Slc6a3; Dat), as well as, dopamine D2 receptor (Drd2) in the olfactory bulb. In contrast, HM aerosols induced the expression of Th and dopamine D5 receptor (Drd5) mRNAs, elicited neuroinflammation and blood-brain barrier-related changes in the olfactory bulb, but did not alter the expression of Omp. Our findings divulge the differential effects of LM and HM aerosols in the brain and suggest that exposure to weld-bonding aerosols can potentially elicit neurotoxicity following a short-term exposure. However, further investigations are warranted to determine if the aerosols generated by weld-bonding can contribute to persistent long-term neurological deficits and/or neurodegeneration.

Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats.

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m³ to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline R(L) was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased R(L) and result in endothelial dysfunction, but otherwise had minor effects on the lung.

Development and characterization of a resistance spot welding aerosol generator and inhalation exposure system.

Limited information exists regarding the health risks associated with inhaling aerosols that are generated during resistance spot welding of metals treated with adhesives. Toxicology studies evaluating spot welding aerosols are non-existent. A resistance spot welding aerosol generator and inhalation exposure system was developed. The system was designed by directing strips of sheet metal that were treated with an adhesive to two electrodes of a spot welder. Spot welds were made at a specified distance from each other by a computer-controlled welding gun in a fume collection chamber. Different target aerosol concentrations were maintained within the exposure chamber during a 4-h exposure period. In addition, the exposure system was run in two modes, spark and no spark, which resulted in different chemical profiles and particle size distributions. Complex aerosols were produced that contained both metal particulates and volatile organic compounds (VOCs). Size distribution of the particles was multi-modal. The majority of particles were chain-like agglomerates of ultrafine primary particles. The submicron mode of agglomerated particles accounted for the largest portion of particles in terms of particle number. Metal expulsion during spot welding caused the formation of larger, more spherical particles (spatter). These spatter particles appeared in the micron size mode and accounted for the greatest amount of particles in terms of mass. With this system, it is possible to examine potential mechanisms by which spot welding aerosols can affect health, as well as assess which component of the aerosol may be responsible for adverse health outcomes.

Nanoparticles-containing spray can aerosol: characterization, exposure assessment, and generator design.

This is the first report demonstrating that a commercially available household consumer product produces nanoparticles in a respirable range. This report describes a method developed to characterize nanoparticles that were produced under typical exposure conditions when using a consumer spray product. A well-controlled indoor environment was simulated for conducting spray applications approximating a human exposure scenario. Results indicated that, while aerosol droplets were large with a count median diameter of 22 µm during spraying, the final aerosol contained primarily solid TiO(2) particles with a diameter of 75 nm. This size reduction was due to the surface deposition of the droplets and the rapid evaporation of the aerosol propellant. In the breathing zone, the aerosol, containing primarily individual particles (>90%), had a mass concentration of 3.4 mg/m(3), or 1.6 × 10(5) particles/cm(3), with a nanoparticle fraction limited to 170 µg/m(3), or 1.2 × 10(5) particles/cm(3). The results were used to estimate the pulmonary dose in an average human (0.075 µg TiO(2) per m(2) alveolar epithelium per minute) and rat (0.03 µg TiO(2)) and, consequently, this information was used to design an inhalation exposure system. The system consisted of a computer-controlled solenoid ''finger'' for generating constant concentrations of spray can aerosols inside a chamber. Test results demonstrated great similarity between the solenoid ''finger''-dispersed aerosol compared to human-generated aerosol. Future investigations will include an inhalation study to obtain information on dose-response relationships in rats and to use it to establish a No Effect Exposure Level for setting guidelines for this consumer product.

Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats.

Many welders have experienced bronchitis, metal fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of welding fume exposure. The objective was to assess the early effects of stainless steel (SS) welding fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS welding fume at a concentration of 15 or 40 mg/m(3) x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses, some animals were intratracheally inoculated with 5x10(4) Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generated fume to be 0.255 microm. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS welding fume caused significant lung damage and suppressed lung defense responses to bacterial infection, but had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS welding fume exposure.

Design, construction, and characterization of a novel robotic welding fume generator and inhalation exposure system for laboratory animals.

Respiratory effects observed in welders have included lung function changes, metal fume fever, bronchitis, and a possible increase in the incidence of lung cancer. Many questions remain unanswered regarding the causality and possible underlying mechanisms associated with the potential toxic effects of welding fume inhalation. The objective of the present study was to construct a completely automated, computer-controlled welding fume generation and inhalation exposure system to simulate real workplace exposures. The system comprised a programmable six-axis robotic welding arm, a water-cooled arc welding torch, and a wire feeder that supplied the wire to the torch at a programmed rate. For the initial studies, gas metal arc welding was performed using a stainless steel electrode. A flexible trunk was attached to the robotic arm of the welder and was used to collect and transport fume from the vicinity of the arc to the animal exposure chamber. Undiluted fume concentrations consistently ranged from 90-150 mg/m(3) in the animal chamber during welding. Temperature and humidity remained constant in the chamber during the welding operation. The welding particles were composed of (from highest to lowest concentration) iron, chromium, manganese, and nickel as measured by inductively coupled plasma atomic emission spectroscopy. Size distribution analysis indicated the mass median aerodynamic diameter of the generated particles to be approximately 0.24 microm with a geometric standard deviation (sigma(g)) of 1.39. As determined by transmission and scanning electron microscopy, the generated aerosols were mostly arranged as chain-like agglomerates of primary particles. Characterization of the laboratory-generated welding aerosol has indicated that particle morphology, size, and chemical composition are comparable to stainless steel welding fume generated in other studies. With the development of this novel system, it will be possible to establish an animal model using controlled welding exposures from automated gas metal arc and flux-cored arc welding processes to investigate how welding fumes affect health.

Model predictions of the recruitment of lung units and the lung surface area-volume relationship during inflation.

Experimental evidence suggests that the lung behaves as if it is composed of a large population of units which are recruited and derecruited during lung expansion and contraction. This study combines two previous models in order to estimate the probability distribution function describing lung unit opening pressures and the resulting alveolar surface area-volume relationship of the excised rat lung during inflation. Results indicate that the opening pressures of lung units during inflation can be described by a normal distribution. The end-expiratory pressure (EEP) has a large effect on the number of lung units that open during inflation and the properties of the area-volume relationship of the lung, but the distribution of opening pressures of individual lung units is fairly consistent regardless of EEP. This study also presents evidence that when the normalized lung area-volume relationship is represented by the equation [A(L)]N = [phiV(L)]N(n) during inflation from the closed state, the expansion coefficient n is between 0.86 and 1. This result supports the theory that, for inflation from EEPs below 4 cmH2O, lung expansion occurs in part by the recruitment of lung units and not solely by the expansion of open units.